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Parkinson’s patients good at automated tasks--study
Sunday, September 05, 2010
Findings of a latest Queen’s research have proposed that individuals suffering from the Parkinson’s disease have better ability of performing programmed, automated errands than the normal people. But Parkinson’s patients encountered difficulty when switching from simple to complex tasks, the researchers found. A team of researchers from the Queen's Center for Neuroscience Studies initiated the present study that hoped to develop a better understanding of the ailment that affects the cognitive functioning of the brain. "We often think of Parkinson's disease as being a disorder of motor function," Douglas Munoz, director of the Center and a Canada Research Chair in Neuroscience said. "But the issue is that the same circuit can affect more cognitive functions like planning and decision-making.” Study details
For the study, the researchers conducted examination on people suffering from the Parkinson’s disease and a control group of normal people. All the study subjects were asked to look at a light, and it was observed that Parkinson’s patients performed much better than the normal candidates. But, when the people were asked to look away from the light, the first group faced difficulty. Ian Cameron, a PhD student at the Queen’s institute, is of the opinion that the findings of the study not only point out that the cognitive balance of the patients was affected due to the medications, but also showed the patient getting upset when asked to perform an alternate task. The researchers are now further working to find out which part of the brain is affected by the currently available drugs that are prescribed to people suffering from Parkinson’s disease. “Functional brain imaging in Parkinson’s patients will be used to help out in this study,” revealed Cameron. The findings of the study have been published in an international interdisciplinary journal of cognitive and behavioural neuroscience, ‘Neuropsychologia’. by Yashika kapoo
Genetic link between Parkinson’s disease and immune system
Friday, August 20, 2010
Researchers have found a new association between Parkinson’s disease and the human leukocyte antigen (HLA) region, which contains a large number of genes related to the function of the immune system in humans. The new findings will encourage further study into the possible role of infections, inflammation and autoimmunity in Parkinson’s disease. HLA genesHLA genes are essential for recognising foreign invaders from the body’s own tissues. Similarly, HLA molecules are supposed to recognise a body’s own tissue and prevent immune reactions against them. However, the system does not always work perfectly, the researchers explain. HLA genes vary greatly from person to person. Certain variants of the genes are associated with increased risk of, or protection against, infectious disease. Other variants can cause autoimmune disorders in which the immune system attacks the body’s own tissues. For example, multiple sclerosis, a neurological disease caused by autoimmunity, is also associated with an HLA gene. The generic variant that is associated with Parkinson’s disease is in the same region as the one associated with multiple sclerosis. People who take non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofenhave a reduced risk of developing Parkinson’s disease, which supports the theory of an immune-related mechanism, the researchers note. However, the protective effect of NSAIDs is not the same for everyone, probably because of genetic differences. Also, NSAIDs can have side effects. Pursuing the connection between Parkinson’s disease and inflammation, especially in the context of variable genetic make-up, may lead to better, more selective medicines for treating the disease, according to the researchers. The study assessed 2,000 participants with Parkinson’s disease and 2,000 healthy volunteers for clinical, genetic and environmental factors that might contribute to the development of Parkinson’s disease and its complications. Some of the subjects were tracked for almost two decades. The study was conducted by the NeuroGenetics Research Consortium, an international team of researchers, and is published online in Nature Genetics. More convincing evidence of link with immune function“Over the years, there have been subtle hints that immune function might be linked to Parkinson’s disease,” says Dr Cyrus Zabetian, a clinical director for the study. “But now we have much more convincing evidence of this and a better idea of which parts of the immune system might be involved.” The study results also point to several other genes that might play a role in the development of Parkinson’s disease. These findings will have to be confirmed and the research team will now study the data even more for gene-environment interactions, with the goal of finding environmental triggers and protectors to develop genetically personalised therapeutics for the treatment and prevention of Parkinson’s disease. By Moira Dower
WebMD Health News
Calgary microchip 'talks' to brain cells
Tuesday, August 10, 2010
 The neurochip is able to monitor the electrical and chemical dialogue between animal brain cells. (CBC)Calgary researchers have created a microchip that "communicates" with brain cells, a discovery that could help patients with Alzheimer's and Parkinson's diseases. A team at the University of Calgary, led by Naweed Syed, figured out how to refine a so-called neurochip to communicate with animal brain cells. "We have never been able to record the subtle activity from brain cells that we have now because this is actually the last frontier," Syed explained on Tuesday. The new technology, conducted with the National Research Council and published online this month in the journal, Biomedical Microdevices, improves on a previous chip by Syed's team in 2004 that used brain cells from snails. The neurochip is able to monitor the electrical and chemical dialogue between brain cells, and to track subtle changes in brain activity. Accessing those areas means researchers could test drugs to treat several neurological conditions accurately and quickly.  Calgary researchers plan to test drugs using the tiny silicon device embedded with brain cells from patients with epilepsy.(CBC)Laurine Fillo, who was diagnosed with Parkinson's disease eight years ago, takes medication to manage her symptoms but has always hoped for a better solution. "I told my husband probably five years ago: 'Oh, one day they'll develop a microchip that they can implant in my brain and it'll control the symptoms and help me manage this disease,'" she said. The Calgary research gives her something to look forward to. "That's something you sort of have to live with when you have a chronic illness, that there is no cure for, and no cause. If there's no hope, then it's hard to go on on a day-to-day basis." In the coming months, the team from the faculty of medicine plans to begin testing drugs using the tiny silicon device, embedded with a network of brain cells surgically removed from patients with epilepsy. Researchers hope a similar chip can one day allow an amputee to control a robotic arm or leg, something only seen currently in movies. "I can't be too sure I might see that final bionic hybrid, you know that whole Terminator idea that always gets brought up, but for sure we are going to make a lot of progress," said researcher Collin Luk.
Scientists Identify Molecular Mechanism Triggering Parkinson's Disease
Wednesday, August 04, 2010
Scientists have identified a molecular pathway responsible for the death of key nerve cells whose loss causes Parkinson's disease. This discovery not only may explain how a genetic mutation linked to Parkinson's causes the cells' death, but could also open the door to new therapeutic approaches for the malady.
In the study, investigators used an animal model, the common fruit fly, to show that the mutation results in impaired activity of recently discovered molecules called microRNAs, which fine-tune protein production in cells. This impairment, in turn, leads to the premature death of nerve cells specifically involved in the secretion of the brain chemical dopamine. The degeneration of these so-called dopaminergic nerve cells in the brain is a hallmark of Parkinson's.
"MicroRNA, whose role in the body has only recently begun to be figured out, has been implicated in cancer, cardiac dysfunction and faulty immune response," said Bingwei Lu, the study's senior author. "But this is the first time it has been identified as a key player in a neurodegenerative disease."
Parkinson's is a movement disorder characterized outwardly by tremor, difficulty in initiating movement, and postural imbalance and, in the brain, by a massive loss of the dopaminergic nerve cells in areas that fine-tune motor activity. It affects an estimated 1 million people in the United States. The incidence of Parkinson's, rare in younger people, increases dramatically with age, although nobody is sure why. Nor is it known why the most common mutation implicated in Parkinson's — LRRK2 G2019S, found in about one-third of all Parkinson's cases occurring among North African Arabs and North American Ashkenazi Jews — increases the likelihood of contracting the disease.
The new findings show that the LRRK2 mutation trips up the normal activity of microRNAs, resulting in the overproduction of at least two proteins that can cause certain cells, like brain cells, to die.
Understanding how microRNA can go wrong requires an understanding of its relationship to its much longer and better-known cousins, "messenger RNA" (or mRNA) molecules. The latter carry genetic recipes from a cell's DNA to specialized molecular machines that translate the instructions into the proteins that make up a cell. In contrast, a microRNA molecule is a very short string of RNA that doesn't contain instructions for making proteins but that can bind to parts of messenger RNA sequences that complement its own. As a result, the messenger RNA's sequence can no longer be read by the cell's protein-manufacturing apparatus, gumming up assembly of the protein it encodes.
It's only recently that scientists have started to understand microRNA's critical role.
The researchers in Lu's lab conducted their experiments in Drosophila, the fruit fly, which has previously proved itself a useful model for several neurodegenerative disorders, yielding substantial insights into Parkinson's, Alzheimer's and Huntington's diseases. They observed that certain proteins were being produced at higher-than-normal levels in the fly LRRK2 model of Parkinson's disease. What particularly drew their attention were two proteins that are important in regulating cell division. Mature nerve cells, which no longer divide, should not have high levels of these proteins; when they do, they are prone to premature cell death.
The researchers looked at the mRNAs containing the genetic recipes for the two overproduced proteins, and predicted that they would be bound by two specific microRNAs: let-7 and miR-184. When they then manipulated the activities of those two microRNA species in flies' brains, they had results consistent with the damage associated with Parkinson's. Diminishing the activity of let-7 in dopaminergic nerve cells, for example, caused both the increased production of one of the suspect proteins and degeneration of the cells.
The researchers showed that toning down the levels of these two proteins, in itself, prevented dopaminergic nerve cell death in the flies. "The flies no longer got symptoms of Parkinson's," said Lu. "This alone has immediate therapeutic implications. Many pharmaceutical companies are already making compounds that act on these two proteins, which in previous studies have been shown to be associated with cancer. It may be possible to take these compounds off the shelf or quickly adapt them for use in non-cancer indications such as Parkinson's."
The researchers then went a step further, showing how the genetic mutation of LRRK2 caused interference of microRNA molecules' ability to inhibit their target mRNAs. It leads to the disruption of a huge complex of molecular machinery that must operate smoothly in order for microRNA to do its job. This link between the common Parkinson's-producing mutation and consequent microRNA malfunction is a new finding.
"The clinical impact of our findings may be five to 10 years down the road," Lu said. "But their impact on our understanding of the disease process is immediate. We can now start testing compounds in mammals and cultured human dopaminergic cells to see if they can inhibit overproduction of these proteins and stave off dopaminergic cell death." Currently available drugs for Parkinson's disease temporarily alleviate its symptoms but can have undesirable side effects, and they don't prevent dopaminergic cells from dying.
References:
1. Gehrke et al. Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature, 2010; 466 (7306): 637 DOI:10.1038/nature09191
Lasers used to alleviate Parkinson's disease symptoms
Saturday, July 24, 2010
Written and produced by Tim Didion
SAN FRANCISCO (KGO) -- A discovery by researchers at Stanford and the Gladstone Institutes in San Francisco could someday help alleviate the symptoms of Parkinson's disease. They have mapped the pathways of the brain associated with the disease and the key to their breakthrough is laser light. It may not look as dramatic as the light sabers in Star Wars, but Anatol Kreitzer believes this laser someday become a powerful weapon in the war against Parkinson's disease. In his lab at San Francisco's Gladstone Institutes' Kreitzer's team is using lasers to manipulate neural pathways in the mice's brains whose cells have been genetically altered to respond to laser light. A research assistant applies laser light to stimulate the neurons in a sample of living brain tissue, which is magnified on the screen. The data collected has allowed Kreitzer's team to not only map specific neural pathways, but also identify their role in controlling movement. An interruption of that neuron function is believed to play a key role in diseases like Parkinson's. "When we can identify the neural circuitry involved these diseases, then we can target it more specifically with drugs," Kreitzer said. Researchers also believe the lasers could eventually have a more direct use. Not just as a research tool, but as an actual treatment for Parkinson's. The current study builds on the work of Stanford University researcher Dr. Karl Deisseroth. Last year, Deisseroth showed us how he was able to use laser light applied directly to a lab animal's brain to turn its dopamine receptors on and off first by addicting the animal to a substance and then reversing the craving and un-addicting it. "And we use laser light to control, to tune and modify the behavior of brain cells," he said. Collaborating with Deisseroth, the research team at Gladstone used that same technique, to turn neural pathways associated with Parkinson's on and off. "We can do two things: We can actually simulate Parkinson's disease, we can cause mice to freeze. But we can also take mice that have Parkinson's disease and activate another pathway, and we can actually relieve the symptoms of that Parkinson's disease," Kreitzer said. He envisions a day when the lasers might be used as an alternative form of deep brain stimulation. That's a therapy where electrodes which are surgically implanted to help control brain function in Parkinson's patients. "Sometime in the future we can put things like diodes that are in an L.E.D. television, very small. You can imagine implanting those in the brain and using them to active neurons," Kreitzer said. While implanting light sources in the human brain may be years or decades away, the technology is giving researcher their first chance to test out theories of how neural pathways interact. The team believes other neural-based diseases like Huntington's and Tourette's syndrome may also be candidates for research using this laser light technique.
How key circuits in the brain control movement
Saturday, July 10, 2010
A new study that has identified how key circuits in the brain control movement could treat movement related disorders, such as Parkinsons disease. Scientists Anatol Kreitzer, PhD and Karl Deisseroth, MD PhD at the Gladstone Institute of Neurological Disease (GIND) and Stanford University used genetic methods to allow mice to produce a light-sensitive protein in very select group of cells in the brain. Researchers found that the mouse with the fibre optics implanted in the brain moved normally with the laser turned off and froze when the laser was turned on. With the laser off, and the mouses movement was restored. Its not something we can do for just a second, Kreitzer said. We can do this for as long as the laser is on. We generated mice that lacked dopamine, and these mice showed many of the same symptoms found in humans with Parkinsons disease. But when we activated the go pathway in these mice, they began to move around normally again. We restored all of their motor deficits with this treatment, even though the mice still lacked dopamine, he added. The research could be important for treating Parkinsons and also other disorders involving these circuits, such as Huntingtons disease, Tourettes syndrome, obsessive-compulsive disorder, and addiction. The research is published in the journal Nature.
Neurologix Announces Successful Phase 2 Trial of Gene Therapy for Parkinson's Disease
Wednesday, June 23, 2010
Neurologix, Inc. (OTC Bulletin Board: NRGX),today announced positive results in a Phase 2 trial of its investigational gene therapy for advanced Parkinson's disease (PD), NLX-P101. Study participants who received NLX-P101 experienced statistically significant and clinically meaningful improvements in off-medication motor scores compared to control subjects who received sham surgery. In the trial, this benefit was seen at one month and continued virtually unchanged throughout the six month blinded study period. The results also demonstrated a positive safety profile for NLX-P101, with no serious adverse events related to the gene therapy or surgical procedure reported. Patients enrolled in the trial had moderate to advanced PD and were not adequately responsive to current therapies.
Neurologix, Inc., is a clinical-stage biotechnology company dedicated to the discovery, development and commercialization of gene therapies for serious disorders of the brain and central nervous system (CNS). Neurologix's investigational AAV(adeno-associated virus) vector gene therapy, NLX-P101, is a novel,non-dopaminergic approach that uses an inhibitory gene (glutamic acid decarboxylase or "GAD") to selectively alter the neural circuitry affected in PD and, thereby, normalize brain physiology. Neurologix's technology is the only gene therapy strategy currently in development which bypasses the dopamine system.
"We are extremely pleased that years of research by our group with AAV vector gene transfer technology has led to the unprecedented milestone of a statistically significant improvement in a double-blind, placebo-controlled trial of gene therapy for any neurological disorder," said Michael G. Kaplitt,MD, PhD, scientific co-founder of Neurologix, Inc., neurosurgeon, NewYork-Presbyterian Hospital/Weill Cornell Medical Center and Associate Professor and Vice Chairman for Research, Department of Neurological Surgery, Weill Cornell Medical College. "We now have solid scientific evidence to support NLX-P101 as an important, potential treatment for this devastating disease."
Matthew J. During, MD, DSc,Professor of Molecular Virology, Immunology and Medical Genetics,Neuroscience and Neurological Surgery, The Ohio State Medical School,and Professor of Molecular Medicine and Pathology, University of Auckland, New Zealand, and Michael G. Kaplitt, MD, PhD, are the scientific founders of Neurologix, Inc., and have been at the forefront of gene therapy research since 1989. This Phase 2 trial is the result of more than 15 years of progress with their work in AAV gene transfer technology. They were the first to demonstrate that AAV could be an effective gene therapy agent in the brain, which they reported in their landmark Nature Genetics paper in 1994. Drs. During, Kaplitt and colleagues subsequently published additional research demonstrating the beneficial effects of AAV-GAD gene therapy for Parkinson's disease in the journal Science in 2002. Today's findings build upon earlier positive results from the NLX-P101 Phase 1 trial, which was the first ever clinical gene therapy trial for Parkinson's disease. Results oft hat study appeared in 2007 as a cover article in The Lancet and in a second article in the Proceedings of the National Academy of Sciences.
Neurologix and Gene Therapy A Novel Approach to Parkinson's Disease
In Parkinson's disease, patients lose dopamine-producing brain cells,resulting in substantial reductions in the activity and amount of GABA(gamma-aminobutyric acid), the major inhibitory neurotransmitter in the brain. This contributes to an abnormal increase in activity of the subthalamic nucleus (STN) of the brain, a key regulatory center for movement, and causes a dysfunction in brain circuitry responsible for coordinating movement. GABA is made by a gene called glutamic acid decarboxylase, or GAD.
Neurologix's gene therapy approach to PD aims to reset the overactive brain cells to inhibit electrical activity and return brain network activity to more normal levels. The strategy involves restoring GABA and thus improving the patient's motor control by using an AAV vector (a disabled, non-pathogenic virus) to deliver the GAD gene back into the STN. Increasing GAD causes more GABA to be synthesized, thus helping to calm the STN over-activity.
NLX-P101is delivered to the brain through a standard, minimally-invasive surgical procedure that uses similar techniques to those currently employed in traditional surgery for PD. The Neurologix gene therapy procedure, however, does not require general anesthesia nor implantation of a permanent medical device in the brain.
"While dopamine clearly plays a role in Parkinson's disease, dopamine levels in the brain are inherently difficult to control, resulting in sub-optimal treatment outcomes for patients. We believe that by altering chemical targets further downstream in the brain's network that regulates movement, we have the potential to help improve outcomes and restore motor function for patients with advanced Parkinson's disease," added Matthew J. During, MD, DSc, scientific co-founder of Neurologix, Inc.
"Based on this data, we are confident that NLX-P101 has great potential to advance the treatment paradigm for Parkinson's patients, and to eventually offer an important, new therapy for patients with this debilitating disease. The study investigators continue to further evaluate the detailed data and we look forward to its publication or presentation," said Clark A. Johnson, President and Chief Executive Officer of the Company. "Today's news is also important validation for our ongoing development of other technologies for neurological and psychiatric diseases, including our advanced pre-clinical program in epilepsy. Given these results, we would look to pursue a strategic transaction which will maximize value for the Company."
Study Details
This double-blind, multi-center, randomized,sham-procedure-controlled Phase 2 study was designed to evaluate the safety and efficacy of NLX-P101 in patients with moderate to advanced PD who were not well-controlled on available medical therapy. Trial participants were randomized to receive either an infusion of NLX-P101 bilaterally into each subthalamic nucleus, or a sham infusion of a sterile saline solution. Each procedure was carried out under local anesthesia.
The primary measure of efficacy in the study was the difference in off-medication motor scores between the treated and sham groups on the Unified Parkinson's Disease Rating Scale (UPDRS) Part 3(Motor section), which has long been the standard for clinical assessment in Parkinson's disease. All subjects were evaluated at baseline as well as one, three and six months after undergoing surgery.
The trial also showed that NLX-P101 was well-tolerated with no serious adverse events related to the drug or procedure reported. All treated subjects will continue to be monitored for safety for a 12-month period following their surgical procedure.
Parallel brainstem circuit discovery suggests new path in Parkinson's research
Thursday, June 10, 2010
By Paul Francuch
Chicago and Montreal researchers studying thelowly lamprey eel have identified an overlooked nervous system pathwayrunning parallel to known brainstem locomotor command circuitry invertebrates such as birds, fishes and mammals.
The finding isreported in Nature Neuroscience, online May 16, and highlighted in themagazine's "news and views" section.
Simon Alford, University ofIllinois at Chicago professor of biological sciences and the article'scorresponding author, said the role of a neurotransmitter associatedwith this parallel pathway may also suggest new research directions fortreating Parkinson's disease.
Alford, along with his formergraduate student and lead author Roy Smetana, now a University ofPittsburgh resident in psychiatry, worked with Universit de Montraland Universit de Qubec Montral neurobiologist Rjean Dubuc and hispost-doctoral researcher Laurent Juvin in trying to sort out how theneurotransmitter analog muscarine modifies sensory information going tothe brain.
Their work determined that muscarine stimulated neuralactivity, leading to locomotion in the laboratory lampreys.
Thegroup focused its attention on a collection of brainstem neurons thattell the spinal cord to generate motor output that enables walking andother locomotion.
"We started looking at this group of neurons,which in the lamprey are conveniently very large, so they're easy toplant electrodes and record from," said Alford. "We discovered themuscarinic excitation was not working on these cells, but on apreviously unknown group of cells within the brainstem."
What'smore, these newly discovered brainstem neurons showed what Alford calleda "very odd response" to the muscarine.
"Instead of just turningon -- like a synapse turns on a neuron and makes it fire -- when youput muscarine on these cells, they turn on and stay on" for a minute orlonger which he said for a neurological reaction can be a very longtime.
The researchers discovered the actual brainneurotransmitter that activates muscarine receptors -- another chemical,acetylcholine -- sends a signal to these newly discovered brainstemneurons, switching them on for the lengthy minute or so durations.
Alfordsaid the finding opens up new insights into animal locomotion.
"It'sa system for turning on your locomotor system and making you walk orrun in a very coordinated, straight-line fashion sustaining locomotionfor a considerable time," he said. "This simply was not known to existbefore we discovered it."
The role of the neurotransmitteracetylcholine may ultimately suggest new Parkinson's disease treatments.While a key Parkinson's symptom is tremor, an advanced stage symptom isthe inability to start a movement, such as walking. Symptoms associatedwith Parkinson's can be helped by reducing acetylcholine-mediatedneurotransmission in the brain, but little work has focused on brainstemmuscarine receptors in this disease.
"This may be a backdoorfinding into a secondary effect of Parkinson's disease that's not wellstudied because most research emphasis has been on dopamine and thebasal ganglia, a different neurotransmitter and region of the brain,"Alford said.
Major funding for the research came from theNational Institute of Neurological Disorders and Stroke, and theCanadian Institutes of Health Research.
Deep Brain Stimulation Improves Quality of Life in Advanced Parkinson's
Wednesday, June 02, 2010
Megan Brooks
In a randomized, multicenter study of advancedParkinson's disease (PD) patients, those treated with deep brainstimulation (DBS) of the subthalamic nucleus combined with best medicaltherapy had better self-reported quality of life at 1 year than thosetreated with best medical therapy alone.
The surgery groupreported greater improvement in mobility and activities of daily livingafter 1 year and required a third less daily dopaminergic drugs than thecontrol group, according to an article published online in the April 29issue of The Lancet.
The differences noted were "clinicallymeaningful," the study team, with senior study author Keith Wheatley,DPhil, professor of medical statistics, Cancer Research UK ClinicalTrials Unit, University of Birmingham, United Kingdom, concludes in thearticle, "but surgery is not without risk, and targeting of patientsmost likely to benefit might be warranted."
Self-Evaluation ofFunctional Status
The results are from the ongoing PD-SURG trial,a randomized, open-label trial.
The study involved 366well-matched patients with advanced PD for whom current medical therapywas not providing adequate symptom control; 183 were randomly allocatedto DBS plus best medical therapy (178 underwent DBS) and 183 to bestmedical therapy alone. In 174 of the surgery patients, the subthalamicnucleus was the surgical target and 176 procedures were bilateral.
Medicaltherapy could include apomorphine infusion according to local practice,other dopamine agonists, monoamine oxidase type B inhibitors,catechol-O-methyltransferase inhibitors, amantadine, or other drugs forPD symptoms.
The primary endpoint was the patients'self-evaluation of their functional status on the 39-item PDquestionnaire (PDQ-39).
According to the investigators, the meanchange from baseline to 1 year on the PDQ-39 summary index was 5.0points in the surgery group and 0.3 point in the medical therapy group(difference, 4.7 points; 95% confidence interval [CI], 7.6 to 1.8; P =.01).
"The sample size for the trial was based on detecting a10-point difference in the quality of life scale," Dr. Wheatley noted inan email to Medscape Neurology. "Of course, we would have liked alarger benefit, but the observed 5-point benefit is worthwhile forpatients."
Significant differences favoring surgery were alsoseen in the mean change in the PDQ-39 score for mobility (8.9; 95% CI,13.8 to 4.0; P = .0004), activities of daily living (12.4; 95% CI,17.3 to 7.5; P < .0001), and bodily discomfort (7.5; 95% CI, 12.6to 2.4; P = .004). Between-group differences in all other domains ofthe PDQ-39 (eg, social support, cognition and communication) were notsignificant.
Verbal Fluency and Vocabulary
However, in aneditorial published with the study, Maria C. Rodriguez-Oroz, MD, fromUniversity of Navarra in Pamplona, Spain, notes that a more detailedneuropsychological analysis of a subgroup of patients showed a declinein verbal fluency and vocabulary in the DBS group.
Still, at 1year, patients who had the surgery were "better able to get about andperform their normal daily activities," Dr. Wheatley told MedscapeNeurology, "and they needed a lot less medication than the patients inthe medical therapy arm."
Patients in the surgery group weretaking a mean levodopa equivalent dose of 894 mg/day (SD, 568 mg/day) at1 year, whereas those in the medical group were on 1347 mg/day (SD, 585mg/day; P < .0001), a difference of 453 mg/day (95% CI, 328 580),which represents a 34% reduction in mean daily dopaminergic drugrequirement in the surgery group.
At baseline, 45 patients ineach group were taking apomorphine. By 1 year, this had decreased to 13in the surgery group and had increased to 63 in the medical therapygroup.
The findings on the PDQ-39, the study team reports, "weremirrored by clinically meaningful differences on the United Parkinson'sDisease Rating Scale (UPDRS), including the patient-rated UPDRS part IV,which showed substantial benefits of surgery in the time and severityof dyskinesia and off periods the most common reasons for patients tobe considered for surgery."
At 1 year, 75 patients in the surgerygroup vs 21 in the control group reported no waking day dyskinesia and45 and 5, respectively, reported no off time (P < .0001 for both).
Asexpected, DBS was not without risk; 36 (19%) of 178 surgery patientshad 43 surgery-related serious adverse events, most commonly infection.There was 1 unsuccessful suicide attempt after DBS in a patient who had aprevious suicide attempt before the study. There was 1 surgery-relateddeath due to hemorrhage.
Trial Differences, Advantages,Limitations
Dr. Rodriguez-Oroz says 3 aspects of this trial makeit different from previous DBS trials in PD patients: "the trialincludes a larger number of patients, has a longer follow-up, andpermits treatment of patients in both groups with continuous infusion ofapomorphine," which is increasingly being used for PD.
One majorlimitation of the trial, recognized by Dr. Rodriguez-Oroz and the studyteam, is that evaluators were not blinded to treatment allocation.Another, according to Dr. Rodriguez-Oroz, is that reports ofimprovements in dyskinesias and off periods were based on the UPDRScomplications of therapy subsection rather than a "more reliablesource," such as diaries, in which patients could note changes in motorabilities more immediately is another limitation.
A thirdlimitation is that a standard definition of the on state was notspecified; "instead, assessment of whether a patient was in the on statewas left to the judgment of neurologists at each center."
"Anexcellent aspect of this trial is that follow-up will continue to 9years," Dr. Rodriguez-Oroz notes. "This will provide invaluableinformation about the long-term benefit of surgery, especially indifferent subgroups of patients (eg, according to age, disease severity,disease duration, and reason for surgery)."
The study wassupported by funding from the UK Medical Research Council andParkinson's UK. One of the study investigators discloses having receivedtravel grants from Medtronic, and another received reimbursement feesfrom Medtronic for time spent collecting and analyzing data as a memberof the ad hoc adverse event committee for another DBS study. The otherstudy authors have disclosed no relevant financial relationships. Dr.Rodriguez-Oroz discloses that she is on the advisory board of UCB Spain;receives payment for lectures and travel for scientific meetings fromGlaxoSmithKline, UCB, Lundbeck, and Medtronic; and has received paymentfrom Medtronic for teaching.
Voice Analysis May Allow Early Detection of Parkinson's
Tuesday, May 04, 2010
Changes in speech occur before other symptoms, could help speed diagnosis, findings show.
HealthDay News) -- A new voice analysis technique can identify changes in speech associated with the early stages of Parkinson's disease
, a new study has found.
"This is a noninvasive, reliable and accurate technique that only requires the patient to read out a few simple sentences," Shimon Sapir, of the department of communication sciences and disorders at the University of Haifa in Israel, who developed the new test, said in a university news release.
In many cases, Parkinson's disease is diagnosed based on muscle rigidity, tremors, slow movement and loss of balance. But by the time these symptoms are present, the disease is already well-advanced.
Since the muscles controlling voice and speech are affected in most people with Parkinson's disease, Sapir decided to develop an acoustic analysis method that identified differences between the speech of people with Parkinson's disease and healthy people. The method also tracks voice changes that occur in response to treatment or disease progression.
A series of tests showed that the new acoustic analysis technique is effective. The findings were published in a recent issue of the Journal of Speech, Language and Hearing Research.
"Doctors and scientists agree that early diagnosis of Parkinson's disease is important in order to slow down or even prevent the degenerative progress of this disease," Sapir said. "Today no treatment is available to this effect, but when treatment becomes feasible, early diagnosis is going to be crucial. There are various methods of brain imaging for detecting early signs of Parkinson's disease, but these methods are expensive -- particularly when attempting to screen a large population at risk. Hence the importance of developing techniques for early diagnosis that are valid, reliable, non-invasive, simple, readily available and inexpensive."
But Sapir added that "while our initial results are very encouraging, additional studies must be carried out in order to examine the new method. Also, given that the disease and its progression have different effects on individuals, speech analysis must be incorporated into a battery of tests that examine other signs and symptoms of the disease, such as changes in handwriting, cognitive functions, sense of smell, and more."
SOURCE U.S. News Health
Parkinson's disease makes it harder to figure out how other people feel
Thursday, March 11, 2010
Published in Health & Medicine
Scientists are beginning to find out why people with Parkinson's disease often feel socially awkward. Parkinson's patients find it harder to recognize expressions of emotion in other people's faces and voices, report two studies published by the American Psychological Association. One of the studies raises questions about how deep brain stimulation, the best available treatment for patients who no longer respond to medication, more strongly affects the recognition of fear and sadness. A neurodegenerative disorder, Parkinson's causes tremors, stiffness and balance problems, as well as fairly frequent depression and dementia.
In the March issue of Neuropsychology, Heather Gray, PhD, and Linda Tickle-Degnen, PhD, report that people with Parkinson's disease, compared with matched controls, often have difficulty discerning how others are feeling.
Their meta-analysis of 34 different studies using data from 1,295 participants shows a robust link between Parkinson's and specific deficits in recognizing emotions, especially negative emotions, across different types of stimuli and tasks.
The meta-analysis, conducted at Harvard Medical School and Tufts University, found that patients typically had some degree of problem identifying emotion from faces and voices. Further clarification is provided in a second study that showed that deep-brain stimulation, compared with medication, caused a consistently large deficit in the recognition of fear and sadness two key facial expressions that, when understood, aid survival. That study is published in the January issue of Neuropsychology.
Researchers led by Julie Pron, PhD, at the Centre Hospitalier Universitaire de Rennes in France, compared the ability of people with Parkinson's in three different groups to recognize facial emotions: 24 advanced patients implanted with deep-brain stimulators after they didn't respond or were sensitive to oral levodopa (the usual drug for the disease); 20 advanced patients given apomorphine hydrochloride by injection or infusion pump while they waited an implant; and 30 healthy controls.
Researchers tested all participants using standard photographs of facial expression before and three months after they were treated. Before implantation of the stimulators, all participants read facial expressions equally well.
Patients in the surgical group were implanted with stimulators, electrical devices that prod the brain's subthalamic nucleus, a small, lens-shaped structure, to normalize the nerve signals that control movement. This nucleus is part of the basal ganglia system, which is thought to integrate movement, cognition and emotion.
Three months after treatment, only the patients with stimulators not the drug-treated patients or the healthy controls were significantly worse at recognizing fear and sadness. Patients with stimulators confused those expressions with others, such as surprise, or even no emotion. Medicated patients and healthy controls were either accurate about fear and sadness or occasionally mistook them for other negative emotions, such as disgust.
"Having Parkinson's predisposes an individual to errors in emotion recognition," said Gray. "The research in France, along with previous studies, indicates that deep-brain stimulation produces an even more severe deficit."
Why would treating a movement disorder affect the perception of emotions? Implants affect a part of the brain that reaches across functions, so the authors suggested that the same electrical stimulation that calms over-excited motor activity may also somehow inhibit emotional processing. Although the impact of Parkinson's and deep-brain stimulation varies by patient, it's important to understand. "The first step is to educate patients and their close associates about the potential for emotion recognition difficulties, so they can learn to manage some of the social consequences, such as misunderstanding and frustration," said Gray and Tickle-Degnen. The next step might be training in emotion recognition, which they said has shown promise.
According to the National Institutes of Health, deep-brain stimulation is used to treat a variety of disabling neurological symptoms, including Parkinson's and essential tremor, a common neurological movement disorder.
At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications. According to Pron, about 15 percent of Parkinson's disease patients are thought capable of benefiting from the surgery.
Dopamine replacement therapy causes brain dysfunction in patients with Parkinson disease, study says
Wednesday, January 20, 2010
Findings point to dopamine replacement therapy causing dysfunction in specific areas of the brain
Peoplewith Parkinsons Disease are more likely to display abnormal socialbehaviour and make poor decisions in ambiguous circumstances if theyare pathological gamblers, according to research in the January issueof the European Journal of Neurology.
A number of studies havealready associated pathological gambling with Parkinsons, suggestingthat it is a frequent impulse control disorder associated mainly withdopamine replacement therapy.
Researchers from the Raul CarreaInstitute for Neurological Research (FLENI) in Buenos Aires, Argentina,interviewed the immediate relatives of seven Parkinsons patients whowere pathological gamblers. They also interviewed the families of 13patients matched by age, sex, education and disease severity whodid not gamble.
They found that the gamblers were lessco-operative with others, had difficulties making or keeping closerelationships and often did what they wanted, without caring what otherpeople thought.
The researchers also found that the patients inthe pathological gambling group performed worse in the Iowa GamblingTask, which is used to assess decision-making abilities in ambiguous orrisky situations.
The object of this study was to assessdecision-making processes in Parkinsons Disease patients with andwithout pathological gambling by asking them and their relatives totake part in a series of tests says Dr Ramon Leiguarda, an expert incognitive neurology.
We found that the patients in thepathological gambling group were more likely to make poor decisions andselect disadvantageous alternatives more frequently than advantageousalternatives.
The combination of poor decision-making andabnormal social behaviour has led the team to conclude that dopaminereplacement therapy can induce dysfunction in the areas of the brainthat control affective decision making the ventromedial pre-frontalcortex and amygdala-ventral striatum system.
Six of the sevenpathological gamblers who took part in the study were male. At the timeof the study they had an average age of 61 and their average age atdiagnosis was 52.
Six of the patients had no history ofgambling before developing Parkinsons Disease. One patient had playedpoker with friends for 30 years, but his gambling behaviour exacerbatedafter starting dopamine replacement therapy and now included rouletteand horse racing.
The other six participants said that their preferred type of gambling was slot machines.
Fourof the seven displayed other impulse control disorders two were alsocompulsive shoppers and two displayed hypersexuality.
Webelieve that the behaviour highlighted in our study, combined withprevious research into the links between Parkinsons Disease andpathological gambling, point to dopamine replacement therapy causingdysfunction in specific areas of the brain says Dr Leiguarda.
Furtherstudies that assess Parkinsons Disease patients recovering frompathological gambling are needed to better understand thephysiopathology of this impulse control disorder.
Small molecules 'protect cells in Parkinson's disease models'
Monday, January 11, 2010
Parkinson's disease could be fought with small molecules, new research suggests.
Anumber of structurally-similar small molecules appear to be able toprotect cells from alpha-synuclein toxicity in several instances ofParkinson's disease, new research has concluded.
Susan Lundquistand her team at the Whitehead Institute used a form of brewers' yeastinjected with several compounds and found that it was able to fight offParkinson's disease-like cells.
Daniel Tardiff, a post-doctoralresearcher with Ms Lindquist, said that theoretically speaking, if acompound is having a beneficial effect on yeast cells, in a worm and inprimary neurons, it might "actually be a potential therapeutic avenueor drug".
He continued: "Though we started in yeast, one ofthose compounds could actually have some potential for human health inParkinson's disease. That's always a lofty goal."
The upcomingWorld Parkinson Congress will be held in Glasgow from September 28th toOctober 1st 2010 and will provide an international forum for the latestmedical practices, scientific discoveries and carers' initiativesrelated to Parkinson's disease.
Despite Earlier Doubts, Feinstein Study Shows Fetal Transplants May Benefit Parkinson’s Patients Ove
Monday, January 04, 2010
Fetal transplant surgery for Parkinsons disease went on experimentallyfor more than a decade before it was put to the ultimate test in adouble-blind, randomized study. It turned out that only patients under60-years-old showed any benefit, but some also developed uncontrolledjerking movements that washed away hope for the technique. The findingswere the death knell for the promising procedure.
Butscientists involved with brain imaging studies of the fetal transplantrecipients did not put away their study tools. In fact, they keptbringing the Parkinsons patients back into the laboratory to takesnapshots of their brains over time. And what they have now found, andreported in the latest issue of The Journal of Nuclear Medicine (JNM),is that people over age 60 began to show improvements more than a yearafter fetal dopamine cells were infused into the brain region damagedby Parkinsons.
This was totally surprising, said DavidEidelberg, MD, director of the Center for Neurosciences at TheFeinstein Institute for Medical Research in Manhasset, NY. The use offetal transplantation for Parkinsons encountered a good deal ofskepticism after five patients in the study (all under age 60)developed dyskinesias.
Dr. Eidelberg said that theParkinsons community basically forgot about the research and turnedtheir attention to other promising techniques.
There were 33patients, 13 of whom were over age 60 when the cells were infused intotheir brains. It was a double-blinded study so that 19 patientsreceived the fetal cells and 14 others had a sham surgery and wereoffered the fetal cell transplant a year later. But by that time, theword had come out about the devastating side effect (the dyskinesias)and some older people opted out of the second surgery.
TheFeinstein researchers have now looked at the brains of the transplantedpatients two years and four years after the initial infusion of fetalcells. And they learned a few things: Beyond the first five people whodeveloped dyskinesia, none of the other 15 younger people in the studyshowed signs of the troubling side effect. In about 25 percent of thecases, clinical improvement was noted and the transplanted cells werestill working to make the dopamine up to four years later.
Theyalso discovered that the older people gradually got better after thefirst year and that their improvements continued over the long term.The older the brain, the harder it is to integrate the graft, saidDr. Eidelberg. But the PET scans told us that the graft was viable.And it took awhile before the cells worked to improve symptoms.
TheFeinstein group has identified two different brain networks hard hit inthe disease. One is obvious: the motor regions that, when damaged, leadto tremors, rigidity and difficulty initiating movement. The otherpiece relates to cognition and mood, and there are discrete brainregions that worsen over time. In this study, researchers found thatpeople did better overall on motor functions if they entered the studywith their putamen intact putamen is an area of the brain thatgoverns cognition and mood. Dopamine is the key brain chemical in boththese networks and it is critical for motor planning. When dementiasets in, people may have improvements in the motor network, but itisnt observable because their cognitive network is abnormal and theirability to make plans to move is impaired.
The good news, saidDr. Eidelberg, is that the grafts stayed where they were and delivereddopamine to the tissue. The finding is critical as the field moves totransplant other types of cells, including embryonic stem cells ortheir ultimate product.
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